Arthropod maturation inhibitors

ABSTRACT

A number of terpenoid compounds and their epoxides were synthesized and found to prevent insect maturation when applied to insects in an immature stage of growth.

United States Patent 1 Schwarz et al.

[ 3,846,451 Nov. 5, 1974 ARTHROPOD MATURATION INHIBITORS [75] Inventors: Meyer Schwarz, Kensington; Philip E. Sonnet, Bowie; Nobel Wakabayashi, New Carrollton, all of Md.

[73] Assignee: The United States of America as represented by the Secretary of Agriculture, Washington, DC.

[22] Filed: Apr. 6, 1973 [21] Appl. No.: 348,553

Related US. Application Data [62] Division of Ser. No. 104,781, Jan. 7, 1971.

[52] US. Cl 260/348 A, 260/348 R, 260/465.9, 260/482, 260/587, 260/593, 424/278,

424/300, 424/304, 424/331, 424/DIG. 12

[51] Int. Cl C07d l/24 [58] Field of Search 260/348 A [56] References Cited OTHER PUBLICATIONS Science, Vol. 167, (Jan. 9, 1970), pp. 191-192.

Primary Examiner-Norma S. Milestone [57] ABSTRACT 1 Claim, No Drawings ARTHROPOD MATURATION INHIBITORS This is a division, of application Ser. No. 104,781

filed Jan. 7, 1971. l

A purposes, irrevocable, royalty-free license in the invention herein described, throughout the world for all purposes of the United States Government, with the power to grant sublicenses for such purpose, is hereby granted to the Government of the United States of America.

This invention relates to the control of arthropods, especially insects, and more particularly to compounds and to the preparation of compounds which exhibit juvenile hormone activity by stimulation of larval development and inhibition of metamorphosis.

In view of the concern throughout the world regarding the persistence of many insecticides and insecticide residues in our environment and the potential hazard that these materials represent to human populations and furthermore, in view of the fact that many species of insect pests have become resistant or immune to insecticides, the need for more selective agents to meet the problems is evident.

Many of the substances that exhibit juvenile hormone activity possess a terpenoid skeleton. These compounds such as farnesol methyl ether and the juvenile hormone isolated from Hyalphora cecropia (L), methyl 10,1 l-oxido-3,l l-dimethyl-7-ethyl trideca-2,6- dienoate, prevent the formation of sexually mature adults when applied at extremely low dosage levels either topically to the insect in the pupal stage or as a fumigant.

An object of this invention is to provide selective agents for control of insect pests.

Another object is to provide new chemical compounds that prevent insect maturation when applied to insects in an immature stage of growth.

In general, accordingto the present invention compounds of the general formula R2 R: A is 4J=CII or CH;

11 is a. number from 1 to 2;

CH: /CN or 43:0

carbon atoms, are synthesized and found to prevent in- 2 sect maturation when applied to insects in an immature stage of growth.

In the following discussion regarding preparation of the compounds, the compound numbers referred to are the same as thos in the filfi howingjmr mone activity.

Compound 1 is prepared by reacting a carboxylic acid of the formula I I. COOH with an excess of an organo-lithium compound in which the organic group can be alkyl, alkinyl, alkynl or aryl. Compound 3 is then prepared by epoxidation of compound 1 with a peracid. Alternatively I may be prepared from using the Wadsworth-Emmons reaction (J. Amer. Chem. Soc. 83, 1733 (1971) to produce l l l GEN The latter product may then be treated with either an organo-Mg-halogen (Grignard reagent) or an organolithium compound to yield the desired compound I (the organic group is same as above). Compounds 5 and 7 are prepared from the appropriate amines,

NHe

and

respectively and the appropriate chloroformate CICOOR (R, as above), .in the presence of a tertiary base such as triethylamine, which serves as a hydrogen chloride acceptor. The required amines are prepared by reduction of the oximesof the aldehydes.

and

the olefmic precursors 5 and 7' using peracid in an inert 3 solvent. Compound is prepared by the condensation of 1 with a malonic acid derivative in the presence of ammonium acetate (J, Amer. Chem. Soc. 63, 3452 (1941). Again, 11 is obtained by epoxidation of 10 using a peracid.

The present invention provides a method for the control of insects, which comprises contacting the insects with one of the compounds in a sufficient amount to affect the normal development of said insects through their metamorphic stages. The materials may be applied to the site of insect infestations by the same methods that are used to broadcast conventional pesticides, that is, diluting them with inert solid carriers or dissolving them in inert organic solvent or oil, or emulsifying them in water.

The following examples illustrate the present invention.

' EXAMPLE 1 Preparation of 3,7-tridecadien-2-one, l 1,12-epoxy, 4,8,l2-tri-methyl. (Compound 3). To an ice cold suspension of sodium hydride (2,4 g) in 200ml N,N-dimethylformamide was added dropwise with stirring while The mixture was allowed to stand overnight and then it was added to a large excess of cold water and extracted with hexane. The hexane extract was washed with water, dried and evaporated. The residue was fractionally distilled and yielded 15 g of farnesonitrile (bp 9497/0-. 2 mm) which was converted to Compound 1 as follows To an ice cold solution of methyl magnesium iodide, prepared from magnesium (0.6 g) and methyl iodide (4.5 g) in 100 ml anhydrous ethyl ether, was added dropwise 5.4 g farnesonitrile. After the addition was complete the reaction mixture was refluxed -for 2 hours, allowed to stand overnight, and then decomposed by dropwise addition of excess aqueous ammonium chloride. The etherlayer was evaporated andacidification and extraction with ether. An ether solution of the acid (1 g) was treated with an excess of methyl lithium in hexane (5 ml ofa 1.6 molar solution). The ketone, Compound 2 (0.5 g), was obtained after the reaction mixture was decomposed with an aqueous solution of ammonium chloride; followed by evaporation of the ether and molecular distillation (100 (bath)/O.5 mm). Epoxida tion and workup, as described in example 1, yielded Compound 4 which had extremely high juvenile hormone activity.

EXAMPLE 3 Preparation of carbamic acid, 3,7-dimethyl-6,7- epoxy-ethyl ester. (Compound 8). 3,7-Dimethyloct-6- enal (15.4 g) in 50 ml ethyl alchohol was added to a solution of hydroxylamine hydrochloride (7 g) and sodium carbonate (5 g) in ml of water. The mixture was heated on the steambath for 15 minutes and then allowed to cool. Addition of an excess of water yielded 3,7-dimethyloct-6-enal oxime as an oil. The oil was extraded with ether and the organic layer dried and evaporated. The residue was added dropwise to a solution of lithium aluminum hydride (3.8 g) in'380 .ml anhydrous ethyl ether. After refluxing overnight an additional quantity of lithium aluminum hydride (0.78 g) was added to complete the reduction. Decomposition of the reaction mixture with excess aqueous sodium hy- 'an ice cold solution of this amine (1.5 g) and triethylamine (l.l g) in ether (25 ml) was added dropwisea solution of ethyl chloroformate (1.1 g) inether (10 ml). The reaction mixture was allowed to stand overthe residue was distilled to yield'3.0 g of Compound 1 EXAMPLE 2 Preparation of 3,7-Tetradecadien-2-one, 11,12- epoxy-8-ethyl-4,l2-dimethyl. (Compound 4). Methyl- 3,1 1-dimethyl-7-ethyltrideca-2,6,lO-trienoate (Braun et a]. J. Econ. Entomol. 61, 866 (1968) (2 g) was saponified with 1.5 g KOH in ml 80 percent ethanol. The acid was isolated from the reaction mixture by night at room temperature. The triethylamine hydrochloride'was filtered off and the ether solution washed with water, dilute hydrochloric acid, and again with water. The ether solution was dried and, evaporated and the residue distilled to yield 2 g carbamic acid (3,7-dimethyl-6-octenyl)-, ethyl ester (Compound 7),v 'bp 102103/0.1 mm. The ester was epoxidized asde- EXAMPLE 4 Synthesis of 2 '6-dodecadienoic acid, 2-cyano-l0,1 l

dimethyl-, methyl ester (Compound 11). Geranyl' aceton'e (.10 g), methyl cyano acetate (6g), ammonium acetate (2 g) and acetic acid (1 ml) were refluxed in 200 ml benzene using a Dean-Starkwater separator. After 2 hours of refluxing, one additional gram of ammonium acetate was added and the refluxing'continued for -2 ad- 'ditioiialhours. The solution was cooled, washed with" n ExAMPLE 5 Malononitrile l ,5,9-trimethyl-8,9-epoxydec-4- enylidene) (Compound 12). A solution of geranyl acetone (10 g), malononitrile (4 g), ammonium acetate (0.5 g) and aceticacid (0.5 g) is refluxed, using a Dean-Stark trap forl hour. The reaction mixture was allowed to cool, then it was washed with water and TABLE ontlnued q and F benzene m The 1'e$ldue was Juvenile Hormone Activity of Representative Compounds on Tenebrio tilled to yield malonon1tr1le-(1,5,9-tnmethyl, decadimollwrpupae 4,8-enyl1dene) (9 g), bp l20l25/.3 mm. Epoxyda- Minimum weight tion of the above as described previously yielded com- 5 525 5 35:35:;- pound 12 when applied to ically to pupae 0 make the resultant mature insect TABLE 1 incapable of Compound reproduction Juvenile Hormone Activity of Representative Compounds on Tenebrio molitor pupae l0 7 fl) 3. 0

Minimum weiaht W (in g.) of comg lpound rieegezd w en app e opically to pupae to o 1 make the resultant mature insect y\/\/\ incapable of l 5 0 H Compound reproduction o W MM o0ocm l 11 CN 01 0.03 M l o 5 o We claim:

ll 1. A compound of the formula WNAO/ H on; nn on; /CN

cine CH(CH)2C=CH(CH:)2C=C (I) 0 ooocn AAA/w o V or a 0 H 

1. A COMPOUND OF THE FORMULA 